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Genetic links between brain development and brain evolution

Nature Reviews Genetics volume 6, pages 581–590 (2005)Cite this article

Abstract

The most defining biological attribute of Homo sapiens is its enormous brain size and accompanying cognitive prowess. How this was achieved by means of genetic changes over the course of human evolution has fascinated biologists and the general public alike. Recent studies have shown that genes controlling brain development — notably those implicated in microcephaly (a congenital defect that is characterized by severely reduced brain size) — are favoured targets of natural selection during human evolution. We propose that genes that regulate brain size during development, such as microcephaly genes, are chief contributors in driving the evolutionary enlargement of the human brain. Based on the synthesis of recent studies, we propose a general methodological template for the genetic analysis of human evolution.

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Figure 1: Values of the encephalization quotient (EQ) for representative primates and hominids.
Figure 2: Brain magnetic resonance images.
Figure 3: Molecular evolution of ASPM and MCPH1 in primates.
Figure 4: A methodological template for investigating the genetic basis of human brain evolution.

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Acknowledgements

We thank P. Evans, N. Mekel-Bobrov, S. Dorus, R.D. Martin, N.M. Pearson, J.P. Rushton, P.T. Schoenemann, E.J. Vallender, and two anonymous reviewers for stimulating discussions and/or critical comments on the manuscript.

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Authors and Affiliations

  1. Department of Human Genetics, Howard Hughes Medical Institute, University of Chicago, 60637, Illinois, USA

    Sandra L. Gilbert & Bruce T. Lahn

  2. Departments of Human Genetics, Neurology, and Pediatrics, University of Chicago, USA

    William B. Dobyns

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  1. Sandra L. Gilbert
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  3. Bruce T. Lahn
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Correspondence to Bruce T. Lahn.

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Related links

Related links

DATABASES

Entrez

ARFGEF2

ASPM

ATR

BRCA1

BRCT domain

MCPH1

SHH

SLC25A19

OMIM

Seckel syndrome

FURTHER INFORMATION

Gene Ontology

The Lahn Laboratory web site

William Dobyns web site

Glossary

ARTIODACTYLS

These are even-toed ungulates (hoofed mamals).

ATAVISM

The reappearance in an organism of characteristics that are present in the organism's remote ancestors.

BROCA'S AND WERNICKE'S SPEECH AREAS

The cortical regions of the brain that are primarily involved in speech. Broca's area is located in the left frontal lobe, and is required for the production of language. Wernicke's area is located in the left temporal lobe, and mediates the understanding of language.

EFFECTIVE POPULATION SIZE

The size of an idealized population that is stable over time and practises random mating. This size, denoted as Ne, is typically much smaller than the real population size, denoted as N, because individuals in a population do not choose mates at random.

FRONTAL LOBES

The front portion of the brain to which functions such as movement, speech, reasoning, planning, emotions and problem solving map.

GENE ONTOLOGY

A database that classifies genes into functional categories.

HOMINID

A family of bipedal primates that includes humans and related fossil species that post-date the human–chimpanzee divergence.

HYPOTONIA

An abnormal decrease in passive resistance to movement (muscle tone) in the extremities. Hypotonia is typically associated with poor head control and loosely extended arms and legs. It is indicative of diseases of the central nervous system or muscle.

OCCIPITOFRONTAL CIRCUMFERENCE

A measurement of the circumference of the head around the most posterior aspect of the skull (the occiput) to the most anterior portion of the frontal bone (the forehead). It is used to monitor brain growth by comparing the measurement with standard graphs of the expected head size for a given set of ages.

PANCYTOPENIA

A shortage of all types of blood cell, including red and white blood cells, as well as platelets.

PERISSODACTYLS

These are odd-toed ungulates.

PERIVENTRICULAR NODULAR HETEROTOPIA

In the brain, nodules comprising nerve cells and supporting cells (glia) that are abnormally located along the walls of the lateral ventricles. The cells should have migrated from the ventricular wall up to the cortex during embryonic development, but failed to do so.

SENSORIMOTOR CORTEX

The part of cerebral cortex that is directly concerned with movement of the body and perception of stimuli (especially related to touch, pressure, temperature and pain).

SIMIANS

A suborder of primates that contains apes (including humans), Old World monkeys and New World monkeys. Simians are also known as anthropoids or higher primates. The other suborder of primates, prosimians (also known as lower primates), is characterized by more primitive features. Prosimians are considered to be basal to simians.

SPASTICITY

An abnormal increase in muscle tone, which might be associated with loss of strength and coordination in voluntary movement. It is a common complication of cerebral palsy, spinal-cord injuries, stroke and some developmental defects of the central nervous system.

2-KETOGLUTARIC ACIDURIA

A disorder of the metabolism whereby elevated concentrations of 2-ketoglutaric acid, a naturally occurring chemical formed as a part of the tricarboxylic acid cycle, are excreted in urine.

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Gilbert, S., Dobyns, W. & Lahn, B. Genetic links between brain development and brain evolution. Nat Rev Genet 6, 581–590 (2005). https://doi.org/10.1038/nrg1634

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